全文获取类型
收费全文 | 548篇 |
免费 | 52篇 |
专业分类
600篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 7篇 |
2021年 | 9篇 |
2020年 | 3篇 |
2019年 | 9篇 |
2018年 | 10篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 31篇 |
2014年 | 23篇 |
2013年 | 44篇 |
2012年 | 47篇 |
2011年 | 43篇 |
2010年 | 27篇 |
2009年 | 30篇 |
2008年 | 23篇 |
2007年 | 35篇 |
2006年 | 37篇 |
2005年 | 29篇 |
2004年 | 24篇 |
2003年 | 36篇 |
2002年 | 35篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 15篇 |
1997年 | 8篇 |
1996年 | 10篇 |
1995年 | 5篇 |
1994年 | 7篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1982年 | 1篇 |
排序方式: 共有600条查询结果,搜索用时 15 毫秒
61.
Kiermer V 《Nature methods》2005,2(10):730
A team from Harvard University has demonstrated that human embryonic stem cells have the capacity to reprogram an adult cell nucleus, leading to a new way of deriving human embryonic stem cell lines without using oocytes. 相似文献
62.
Durá MA Receveur-Brechot V Andrieu JP Ebel C Schoehn G Roussel A Franzetti B 《Biochemistry》2005,44(9):3477-3486
Pyrococcus horikoshii open reading frame PH1527 encodes a 39014 Da protein that shares about 30% identity with endoglucanases and members of the M42 peptidase family. Analytical ultracentrifugation and electron microscopy studies showed that the purified recombinant protein forms stable, large dodecameric complexes with a tetrahedral shape similar to the one described for DAP, a deblocking aminopeptidase that was characterized in the same organism. The two related proteins were named PhTET1 (for DAP) and PhTET2 (for PH1527). The substrate specificity and the mode of action of the PhTET2 complex were studied in detail and compared to those of PhTET1 and other assigned M42 peptidases. When assayed with short chromogenic peptides, PhTET2 was found to be an aminopeptidase, with a clear preference for leucine as the N-terminal amino acid. However, the enzyme can cleave moderately long polypeptide substrates of various compositions in a fairly unspecific manner. The hydrolytic mechanism was found to be nonprocessive. The enzyme has neither carboxypeptidase nor endoproteolytic activities, and it is devoid of N-terminal deblocking activity. PhTET2 was inhibited in the presence of EDTA and bestatin, and cobalt was found to be an activating metal. The PhTET2 protein is a highly thermostable enzyme that displays optimal activity around 100 degrees C over a broad pH array. 相似文献
63.
64.
Aardema MJ Snyder RD Spicer C Divi K Morita T Mauthe RJ Gibson DP Soelter S Curry PT Thybaud V Lorenzon G Marzin D Lorge E 《Mutation research》2006,607(1):61-87
In this report, results are presented from an international study of the in vitro micronucleus assay using Chinese hamster ovary cells. This study was coordinated by an organizing committee supported by the SFTG (the French branch of the European Environmental Mutagen Society). Test chemicals included mannitol, bleomycin, cytosine arabinoside, urethane and diethylstilboestrol. Mitomycin C was used as a positive control. Each chemical was evaluated in at least two laboratories following a variety of different protocols (short and long exposures, varying recovery times, with and without cytochalasin B) in order to help determine a standard protocol for routine testing in Chinese hamster ovary cells. Mannitol and urethane were negative, while bleomycin, cytosine arabinoside and diethylstilboestrol induced a dose dependent increase in micronucleated cells. In the presence of cytochalasin B, increases in micronuclei were observed in binucleated as well as mononucleated cells in cultures treated with bleomycin, cytosine arabinoside or diethylstilboestrol. Importantly, all three of these chemicals were detected in each of the different treatment/recovery regimens. No differences were seen in the sensitivity or accuracy of the responses in the presence of absence of cytochalasin B. Overall, these results demonstrate the suitability of Chinese hamster ovary cells for the in vitro micronucleus assay. 相似文献
65.
Eyong KO Folefoc GN Kuete V Beng VP Krohn K Hussain H Nkengfack AE Saeftel M Sarite SR Hoerauf A 《Phytochemistry》2006,67(6):605-609
The study of the chemical constituents of the roots of Newbouldia laevis (Bignoniaceae) has resulted in the isolation and characterization of a naphthoquinone-anthraquinone coupled pigment named newbouldiaquinone A (1) together with 14 known compounds: apigenin, chrysoeriol, newbouldiaquinone, lapachol, 2-methylanthraquinone, 2-acetylfuro-1,4-naphthoquinone, 2,3-dimethoxy-1,4-benzoquinone, oleanolic acid, canthic acid, 2-(4-hydroxyphenyl)ethyl triacontanoate, newbouldiamide, 5,7-dihydroxydehydroiso-alpha-lapachone, beta-sitosterol, and beta-sitosterol glucopyranoside. The structure elucidation of the isolated compounds was established based on spectroscopic studies, notably of the 2D NMR spectra. The antimalarial activity of compound (1) against Plasmodium falciparum in vitro shows moderate chemo suppression of parasitic growth. Its antimicrobial activity against a wide range of microorganisms was 13- and 24-fold more active against Candida gabrata and Enterobacter aerogens than the reference antibiotics nystatin and gentamycin. 相似文献
66.
Understanding the biological principles behind virus-induced symptom expression in plants remains a longstanding challenge. By dissecting the compatible host-virus relationship temporally and genetically, we have begun to map out the relationships of its component parts. The picture that emerges is one in which host gene expression and physiology are under tight temporal control during infection. 相似文献
67.
68.
Verhoeven VJ Hysi PG Saw SM Vitart V Mirshahi A Guggenheim JA Cotch MF Yamashiro K Baird PN Mackey DA Wojciechowski R Ikram MK Hewitt AW Duggal P Janmahasatian S Khor CC Fan Q Zhou X Young TL Tai ES Goh LK Li YJ Aung T Vithana E Teo YY Tay W Sim X Rudan I Hayward C Wright AF Polasek O Campbell H Wilson JF Fleck BW Nakata I Yoshimura N Yamada R Matsuda F Ohno-Matsui K Nag A McMahon G Pourcain BS Lu Y Rahi JS Cumberland PM Bhattacharya S Simpson CL Atwood LD Li X Raffel LJ Murgia F Portas L 《Human genetics》2012,131(9):1467-1480
Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations. The study population comprised 31 cohorts from the Consortium of Refractive Error and Myopia (CREAM) representing 4 different continents with 55,177 individuals; 42,845 Caucasians and 12,332 Asians. We performed a meta-analysis of 14 single nucleotide polymorphisms (SNPs) on 15q14 and 5 SNPs on 15q25 using linear regression analysis with spherical equivalent as a quantitative outcome, adjusted for age and sex. We calculated the odds ratio (OR) of myopia versus hyperopia for carriers of the top-SNP alleles using a fixed effects meta-analysis. At locus 15q14, all SNPs were significantly replicated, with the lowest P value 3.87?×?10(-12) for SNP rs634990 in Caucasians, and 9.65?×?10(-4) for rs8032019 in Asians. The overall meta-analysis provided P value 9.20?×?10(-23) for the top SNP rs634990. The risk of myopia versus hyperopia was OR 1.88 (95?% CI 1.64, 2.16, P?0.001) for homozygous carriers of the risk allele at the top SNP rs634990, and OR 1.33 (95?% CI 1.19, 1.49, P?0.001) for heterozygous carriers. SNPs at locus 15q25 did not replicate significantly (P value 5.81?×?10(-2) for top SNP rs939661). We conclude that common variants at chromosome 15q14 influence susceptibility for myopia in Caucasian and Asian populations world-wide. 相似文献
69.
Nogueira V Sundararajan D Kwan JM Peng XD Sarvepalli N Sonenberg N Hay N 《The EMBO journal》2012,31(5):1134-1146
The requirement of Akt for cell proliferation and oncogenesis is mammalian target of rapamycin complex 1 (mTORC1) dependent. SV40 large T expression in Akt-deficient cells restores cell proliferation rate, but is insufficient for exiting contact inhibition and oncogene-induced anchorage-independent growth, because of a failure to promote Skp2 mRNA translation. Skp2 mRNA and protein are induced upon exiting contact inhibition, which enables entry into mitosis. While Skp2 mRNA is induced in Akt-deficient cells, it is not translated, preventing entry into mitosis. Restoring Skp2 expression in Akt-deficient cells is sufficient to restore exit from contact inhibition and oncogenesis. Skp2 mRNA translation is dependent on mTORC1 and the eukaryotic translation initiation factor 4E (eIF4E). Thus, the requirement of Akt for exiting contact inhibition is mediated by the induction of Skp2 mRNA translation in eIF4E-dependent mechanism. These results provide a new insight into the role of the Akt/mTORC1/eIF4E axis in tumourigenesis. Akt-dependent Skp2 mRNA translation is also required for mitotic clonal expansion (MCE)--the earliest event in adipogenesis. Skp2 re-expression in Akt-deficient preadipocytes, which are impaired in adipogenesis, is sufficient to restore adipogenesis. These results uncover the mechanism by which Akt mediates adipogenesis. 相似文献
70.
Andrews MJ Clase JA Bar G Tricarico G Edwards PJ Brys R Chambers M Schmidt W MacLeod A Hirst K Allen V Birault V Le J Harris J Self A Nash K Dixon G 《Bioorganic & medicinal chemistry letters》2012,22(6):2266-2270
MAPKAPK5 has been proposed to play a role in regulation of matrix metalloprotease expression and so to be a potential target for intervention in rheumatoid arthritis. We present here the identification of a series of compounds against this target which are effective in both biochemical and cell assays. The expansion of the series is described, along with early SAR and pharmacokinetics for some representative compounds. 相似文献